Chloromethyl Methyl Ether → 2-Fluoro-3-(methoxymethoxy)pyridine

2-Fluoropyridin-3-ol (55 g, 486 mmol) and cesium carbonate (158 g, 486 mmol) were suspended in ACN (400 mL). A solution of chloromethyl methyl ether (40 mL, 527 mmol) in dry tetrahydrofuran (50 mL) was added dropwise via an addition funnel. After 1 hour additional MOM-Cl (5 mL) was added and the reaction stirred for another 2 h. The reaction was evaporated to dryness under reduced pressure and the residue partitioned between diethyl ether (400 mL) and water (500 mL). The organic was washed with saturated sodium bicarbonate (100 mL) then dried with magnesium sulfate and evaporated to dryness under reduced pressure. The crude was purified using silica chromatography (hexane to 1:1 hexane:DCM gradient) to give the desired 2-fluoro-3-(methoxymethoxy)pyridine (53.5 g, 340 mmol, 70.0% yield).

1. customThe reaction was evaporated to dryness under reduced pressure
2. customthe residue partitioned between diethyl ether (400 mL) and water (500 mL)
3. washThe organic was washed with saturated sodium bicarbonate (100 mL)
4. dry with materialthen dried with magnesium sulfate
5. customevaporated to dryness under reduced pressure
6. customThe crude was purified

ORD record

ord-08a6d2faf40242e7ab3b8f92ceb337ef

Source dataset

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08883782B2